(Applicant's Abstract): Despite the availability of numerous medications to treat inflammatory conditions such as arthritis, asthma and inflammatory bowel disease, treatments are not ideal. The toxicity of the steriodal and non-steroidal anti-flammatory agents (NSAID) can be devastating to the overall health and quality of life of these individuals. NSAID can cause severe gastric ulcers requiring surgery; corticosteroids can cause severe toxic effects to the bone, muscle and endocrine systems and psychic disturbances such as euphoria, hallucinations and mental depression. Some patients with inflammatory conditions are resistant to medications and require long-term treatment with large doses, which further increases the toxic potential. Because of these limitations to inflammatory disease treatment, patients are increasingly looking for safe and natural alternatives. Traditionally, Indian Medicine (Ayurvedic Medicine) has used several combinations of botanicals to treat inflammatory conditions such as arthritis and respiratory illnesses. These combinations commonly include Curcuma longa rhizome (powdered turmeric root), Zingiber officinale rhizome (powdered ginger root) and the gum resin of Boswellia serrata. Very little data exist to support the efficacy or safety of these products. Before clinical trials can be undertaken however, more needs to be known about the human pharmacokinetic or pharmacodynamic properties of these products. The long range goal of this project is to determine the basic pharmacodynamic properties of these products. The long range goal of this project is to determine the basic pharmacokinetics and pharmacodynamics of anti-inflammatory botanical dietary supplements (ABDS) to provide the information needed to target appropriate inflammatory conditions in phase II and phase III studies using appropriate doses and intervals. The information obtained will also help predict drug interactions both positive and negative among the botanicals and combining these botanicals with conventional medicines. This project proposes to assess the pharmacokinetic and pharmacodynamic characteristics of three commonly used Ayurvedic ABDS. The primary aims and hypotheses for this four year study (years 2 to 5 of the grant) include the following: 1. Evaluate the pharmacokinetics of turmeric, ginger, and boswellia alone and in combination. Hypothesis A: Normal healthy volunteers will show equal bioavailability of individual components to achieve measurable serum concentrations and pharmacological activity. Hypothesis B: Normal healthy volunteers will show equal bioavailability of individual components when turmeric, ginger or boswellia are combined. 2. Evaluate the pharmacodynamics of turmeric, ginger and boswellia. Hypothesis C: Dose normalized peak serum concentrations (Cmax) and the area under the curve (AUC) will be equivalent for varied doses of turmeric, ginger and boswellia. Hypothesis D: Blood taken from normal healthy volunteers and stimulated with lipopolysaccharide (LPS) will show inhibition of one or more key inflammatory cytokines including tumor necrosis factor alpha (TNFalpha), interleukin-1 (IL-1), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) and increased production of an anti-inflammatory cytokine, interleukin-10 (IL-10), after the oral ingestion of turmeric, ginger or boswellia taken singly or in combination. 3. Evaluate the platelet inhibiting effects of turmeric, ginger and boswellia. Hypothesis E: Bleeding times measured before and after the ingestion of turmeric, ginger, or boswellia, or combinations of these botanicals are equivalent. Our expectations are that this information will help design future clinical trials utilizing turmeric, ginger and boswellia in humans. The pharmacokinetic information will help guide dosing and help predict the potential for drug interactions and contraindications. The pharmacodynamic information will help guide which inflammatory diseases are likely to be responsive to treatment with these ABDS. The principal investigators will be collaborating with recognized experts in the field of inflammatory diseases (Dr. Michael Maurice, see letter of support) and integrative medicine (Dr. Andrew Weil, see letter of support). This collaboration will serve as a needed bridge between the basic sciences, i.e. in vitro and animal testing and clinical testing in humans. One of the primary reasons we have chosen to begin our studies of ABDS with turmeric, ginger and boswellia is that Dr. Weil recommends these botanicals to his patients with rheumatoid arthritis. He has clinical experience showing the potential for efficacy, but recognizes the need for further research to demonstrate what are the most effective products, doses and dosage forms Also, since these products have traditionally been used for other inflammatory diseases such as asthma and inflammatory bowel disease, he further recognizes the need for testing in area outside of his clinical experience that may ultimately benefit patients. Drs. Maricic and Weil will provide the clinical expertise in providing physician services in this Phase I trial and will help us design and recruit patients for subsequent clinical trials in Phase II testing.